Homology modelling is used in order to
predict the 3 dimensional structures of proteins with unknown 3D
structure, using solved homologous proteins as templates.

Homology modelling claims that the
biological structure of a protein is more related to its biological
properties and function than its sequence. A homologous protein is a
protein that belongs to the same family, has the same function and
shares more than thirty percent similarity with the protein of
interest.

The first step of a homology modelling
algorithm is to set up and optimise the sequence alignment between
the query protein and its template. Sequence alignment is broken down
into four steps. Firstly, it uses rapid alignment methods to
calculate all pairwise similarity scores. The second step is the
generation of a similarity matrix. Then the sequences are clustered
according to the generated similarity matrix with the aid of an
algorithm. The next step is the generation of a cluster alignment
using a consensus method and finally a multiple-progressive alignment
is generated. The groups of the sequences are aligned according to
their cluster branch order.

After that the algorithm will perform an
initial partial geometry alignment for the sequence of the template
protein with the unknown structure. The initial geometry will be
copied from various regions of one or more template proteins. If
there is residue identity, between the alignments, then all
coordinates are copied. That includes backbone and sidechain. If
there is not residue identity but still residue similarity is
retained, only the coordinates from the backbone atoms will be passed
on. In cases of zero identity or similarity a gap will be left on the
model, which is also known as loop. A loop will be modelled by
borrowing coordinates from any protein (from the Protein Data Bank)
that matches the required sequence. The sidechain is generated
automatically using a build-in rotamer explorer module.

Finally, the new models must adequately
meet and satisfy a scoring function that ensures that the degrees of
the non-polar sidechain groups that are buried are within range and
that all hydrogen bonding capabilities have been explored.